CN105636446A - Herbicidal composition comprising acc inhibitors - Google Patents

Herbicidal composition comprising acc inhibitors Download PDF

Info

Publication number
CN105636446A
CN105636446A CN201480057195.1A CN201480057195A CN105636446A CN 105636446 A CN105636446 A CN 105636446A CN 201480057195 A CN201480057195 A CN 201480057195A CN 105636446 A CN105636446 A CN 105636446A
Authority
CN
China
Prior art keywords
alkyl
thioether
under
existence
prepared
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201480057195.1A
Other languages
Chinese (zh)
Other versions
CN105636446B (en
Inventor
Q·杨
B·洛尔斯巴赫
G·惠特克
C·迪米西斯
K·格雷
Y·张
J·M·穆胡希
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Corteva Agriscience LLC
Original Assignee
Dow AgroSciences LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dow AgroSciences LLC filed Critical Dow AgroSciences LLC
Publication of CN105636446A publication Critical patent/CN105636446A/en
Application granted granted Critical
Publication of CN105636446B publication Critical patent/CN105636446B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/38—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/38—Nitrogen atoms
    • C07D231/40—Acylated on said nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S424/00—Drug, bio-affecting and body treating compositions
    • Y10S424/10—Insect repellent

Abstract

The present application provides efficient and economical synthetic chemical processes for the preparation of pesticidal compounds and compounds useful both as pesticides and in the making of pesticidal compounds such as pesticidal thioethers and pesticidal sulfoxides efficiently and in high yield from commercially available starting materials. Further, the present application relates to certain novel compounds necessary for their synthesis.

Description

The method preparing Pesticidal compound
The cross reference of related application
This application claims and benefit from following U.S. earlier application: the series number No.62/034,456 submitted to on 08 07th, 2014; The series number No.62/001 submitted to on 05 22nd, 2014, the series number No.61/892 that on October 17th, 925 and 2013 submits to, the application of 124, these whole disclosures of application are therefore clear and definite to be incorporated herein by list of references.
Technical field
The synthesis chemical method of the efficient and cost-effective that the application relates to insecticidal thioethers and prepared by parasite killing sulfoxide. Additionally, the application further relates to for some compounds necessary to their synthesis. From commercially available initiation material, effectively and high productivity prepares insecticidal thioethers and parasite killing sulfoxide will be advantageous for.
Describe in detail
Defined below being applied to runs through the term that this specification uses, unless otherwise the restriction of particular example.
Just as used in the present invention, term " alkyl " represents the hydrocarbon chain of branching or non-branching.
Just as used in the present invention, term " alkynyl " represents the hydrocarbon chain with at least one C �� C branching or non-branching.
Except as otherwise noted, the term " cycloalkyl " being used alone in the present invention is saturated cycloalkyl group, for instance cyclopropyl, cyclobutyl, cyclopenta, cyclohexyl.
Term " sulfur " as another group part refers to the sulphur atom being used as junctional complex between two groups just as used in the present invention.
As in the present invention individually or as another group a part use term " halogen " refer to chlorine, bromine, fluorine and iodine.
The Compounds and methods for of the application is described in detail below in scheme 1.
Scheme 1
In the step a of scheme 1, Isosorbide-5-Nitrae-nitropyrazole carries out halo and reduction to obtain 3-chloro-1H-pyrazoles-4-amine hydrochlorate (1a). By using concentrated hydrochloric acid (37 weight %) that halogenation occurs at 3-carbon place. Carry out reducing (preferably having the palladium on alumina of about 1 to 10 weight %, more preferably about 5 weight %) with triethyl silicane and palladium on alumina. This reaction can carry out at the temperature of about 10 DEG C to about 20 DEG C. This reaction can carry out in polar aprotic solvent, for instance methanol or ethanol, it is preferable that ethanol. It is surprisingly found that, by using about 1 to arrive about 4 equivalents in this step, preferably approximately 2.5 equivalents are to the triethyl silicane of about 3.5 equivalents, simultaneously between about 0 DEG C to about 40 DEG C, react between about 20 DEG C preferably in 10 DEG C, relative to less desirable product
Obtain the desired halogenated product 3-chloro-1H-pyrazoles-4-amine hydrochlorate (1a) of about 10:1 mol ratio
In the step b of scheme 1,3-chloro-1H-pyrazoles-4-amine hydrochlorate (1a) and activated carbonyl thioether reactant, it is expressed as X1C (=O) C1-C4-alkyl-S-R1, to prepare insecticidal thioethers (3a). R1Select free C1-C4Haloalkyl and C1-C4Alkyl-C3-C6The group of halogenated cycloalkyl composition, it is preferable that R1Selected from CH2CH2CF3Or CH2(2,2-difluorocyclopropyl). X1Selected from Cl, OC (=O) C1-C4The group X of alkyl or formation activating carboxy acid1. Work as X1It is Cl or OC (=O) C1-C4During alkyl, this reaction can at alkali, it is preferable that carries out obtaining insecticidal thioethers (3a) under the existence of sodium bicarbonate at the temperature of about-10 DEG C to about 40 DEG C. This reaction can carry out in solvent mixture such as oxolane and water. It is surprisingly found that the thioether (3a) prepared by this synthetic route is only mono acrylic ester, this is because there is cl radical on the 3-position of pyrazole ring. The present invention describes the comparative example not having halogen on 3-position, which gives the product (referring to " CE-1 ") of double methacrylate. Additionally, compared with the product (referring to " CE-2 ") obtained with cl radical, the comparative example on 3-position with bromine group provides product with surprising low-yield.
Optionally, X is worked as1C (=O) C1-C4-alkyl-S-R1It is by such as 2,4,6-tripropyl-three oxygen three phosphinate-2, during the activating carboxy acid that the reagent of 4-trioxide, carbonyl dimidazoles, dicyclohexyl carbon diimidazole or 1-ethyl-3-(3-dimethylaminopropyl) carbon diimidazole activates at the temperature of about 0 DEG C to about 80 DEG C, this reaction can complete; This reaction can also use urea salt or phosphine activated group such as O-(7-azepine benzo triazol-1-yl)-N, N, N ', N '-tetramethylurea salt sulfur fluorophosphoric acid ester or benzotriazole-1-base oxidation tripyrrole quinoline phosphine sulfur fluorophosphoric acid ester, at polar aprotic solvent, such as N, in dinethylformamide, oxolane or dichloromethane, at the temperature of about-10 DEG C to about 30 DEG C, at amine alkali, such as, under the existence of diisopropyl ethyl amine or triethylamine, advance to form insecticidal thioethers (3a). The carbonyl thioether of activation can by X1C (=O) C1-C4-alkyl-S-R1Preparation, wherein X1Being OH, it can pass through to make corresponding ester thioether, is expressed as X1C (=O) C1-C4-alkyl-S-R1, wherein X1It is OC1-C4-alkyl, reacts in polar solvent such as methanol or oxolane with metal hydroxides such as Lithium hydrate and prepares. Optionally, wherein X1It is OH or OC1-C4The X of-alkyl1C (=O) C1-C4-alkyl-S-R13-mercaptopropionic acid and ester thereof can be passed through and 3,3,3-trifluoro propene carries out photochemistry free radical coupling in inert organic solvents under the existence of 2,2-dimethoxy-2-phenyl acetophenone initiator and long wavelength UV light and prepares. Although need the 3-mercaptopropionic acid of stoichiometry or its ester and 3,3,3-trifluoro propenes, but due to its low boiling point, it is common to use 3,3,3-excessive trifluoro propenes are used for compensating regular loss. The initiator of about 10 moles of %, 2,2-dimethoxy-2-phenyl acetophenone, it is preferred to about 5 moles of % are arrived in typical use about 1. Long wavelength UV light is occasionally referred to as " black light " and they are in about 400 to the scope of about 365 nanometers. This photochemistry is coupled in inert organic solvents to carry out. Typical inert organic solvents must remain liquid at about-50 DEG C, and condition of free radical must be kept relative inertness and must dissolve reactant at the reaction temperatures by it. Preferred inert organic solvents is aromatic series and aliphatic hydrocarbon, for instance toluene. React temperature not limit, but generally they are at about-50 DEG C to about 35 DEG C. First, keeping temperature is important lower than the boiling point of 3,3, the 3-trifluoro propenes i.e. temperature of about-18 DEG C to about-16 DEG C. In typical reaction, inert organic solvents is cool below about-50 DEG C and 3,3,3-trifluoro propene bubblings and enters in solvent. Add 3-mercaptopropionic acid or its ester and 2,2 ,-dimethoxy-2-phenyl acetophenone and open long wave function (366nm) UVP lamp (4 watts). After 3-mercaptopropionic acid or its ester fully convert, close lamp and remove solvent.
3-((3,3,3-trifluoro propyl) sulfur) propanoic acid can also pass through 3-mercaptopropionic acid and 3,3,3-trifluoro propene is 2, at the temperature of about-50 DEG C to about 40 DEG C, in inert organic solvents, carry out the coupling of low temperature free radical initiation under the existence of nitrile (V-70) initiator in 2'-azo two (4-methoxyl group-2,4-dimethyl) penta and prepare. Although need the 3-mercaptopropionic acid of stoichiometry or its ester and 3,3,3-trifluoro propenes, but due to its low boiling point, it is common to use 3,3,3-excessive trifluoro propenes are to compensate regular loss. Typical use about 1 to about 10 moles of % initiator V-70, and preferably about 5 moles of %. What low temperature free radical caused is coupled in inert organic solvents to carry out. Typical inert organic solvents remains liquid at must be about-50 DEG C, and radical reaction condition must be kept relative inertness and must dissolve reactant at the reaction temperatures by it. Preferred inert organic solvents is toluene, ethyl acetate and methanol. The temperature reacted is about-50 DEG C to about 40 DEG C. Solution is cool below about-50 DEG C and transferred in reactant mixture by 3,3,3-trifluoro propene. At room temperature stirring 24 hours after, reactant mixture is heated approximately to 50 DEG C about 1 hour to decompose the V-70 initiator of any residual, then cool down and remove solvent.
In the step c of scheme 1, thioether (3a) and haloperidid, preferred 3-pyridine bromide is at mantoquita (such as Cu-lyt. (I), copper chloride (II) and Hydro-Giene (Water Science). (I)), alkali such as potassium phosphate and potassium carbonate, preferred potassium carbonate, and N, N '-dimethyl ethane-1, reacts under the existence of 2-diamidogen to obtain insecticidal thioethers (3b). This synthetic method is simpler relative to known heteraryl method and reduces the cost of initiation material. The method can in polar solvent such as acetonitrile, dioxane or DMF at temperature between about 50 DEG C to about 110 DEG C, it is preferable that carry out at about 70 DEG C to about 90 DEG C. Preferred reaction mixture heats 2 hours to 24 hours while stirring.
In the step d of scheme 1, insecticidal thioethers (3b) preferably uses R2-X2Alkylation is to obtain insecticidal thioethers (3c), wherein X2It it is leaving group. This leaving group can be selected from halogen, methanesulfonates or tosylate. R2Selected from C1-C4-alkyl, C2-C4-alkynyl, it is preferred to methyl, ethyl and propargyl. R2-X2Iodomethane, bromoethane, iodoethane, propargyl chloride, propargyl bromide, ethyl methane sulfonate, the propargyl ester of methanesulfonic acid, toluenesulfonic acid ethyl ester and the propargyl ester of toluenesulfonic acid can be selected from. Alkylated reaction is at inorganic base, under the existence of the carbonate of preferred metal such as cerous carbonate, metal hydroxides, metal phosphate, metal hydride, polar solvent, preferred DMF existence under carry out at the temperature of about 0 DEG C to about 80 DEG C.
Optionally, in the step d of scheme 1, the alkylation of insecticidal thioethers (3b) can at alkali, such as, under the existence of sodium hydride, at polar non-solute, such as, under the existence of DMF, oxolane, hexamethyl phosphoramide, dimethyl sulfoxide, METHYLPYRROLIDONE and sulfolane, carry out at the temperature of about 0 DEG C to about 30 DEG C. It has unexpectedly been discovered that, relative to the C of comparative1-C4-alkyl-S-R1The retro-Michael type of unit (referring to " CE-3 ") eliminates, and uses sulfolane to promote alkylated reaction as solvent. Have been found that the iodide additive using catalysis, for instance potassium iodide or tetrabutylammonium iodide will react necessary time decreased to about 24 hours. Also find that reacting by heating will reduce by about 24 hours in the response time in the reactor (preventing bromoethane from losing) sealed at about 50 DEG C to about 70 DEG C.
In the step e of scheme 1, with hydrogen peroxide (H2O2) thioether (3c) is oxidized to methanol to obtain desired parasite killing sulfoxide (3d).
Embodiment
There are following example better to illustrate the present processes.
Embodiment 13-chloro-1H-pyrazoles-4-amine hydrochlorate (1a):
To being mounted with that the 1000-mL of mechanical agitator, temperature probe and nitrogen inlet, many mouthfuls of circular-cylindrical jacket reactors inject the palladium (5wt%, 2.5g) on 4-nitropyrazole (50.0g, 429mmol) and aluminium oxide. Add ethanol (150mL), then add slowly and do hydrochloric acid (37wt%, 180mL). Reaction being cooled to 15 DEG C, and added triethyl silicane (171mL, 1072mmol) slowly above at 1 hour by charging hopper, being maintained with internal temperature is 15 DEG C. This reaction is stirred 72 hours at 15 DEG C, passes through afterwardsLiner filters reactant mixture and by hot ethanol (40 DEG C, 2 �� 100mL) washing and precipitating. Separate the filtrate merged and water layer (bottom) is concentrated as��100mL. Addition acetonitrile (200mL) and the suspension obtained are worked overtime 1 hour at 20 DEG C and filter. With acetonitrile (2 �� 100mL) clean filter cake and at 20 DEG C dry to provide white solid (mixture of 1a and the 1H-pyrazoles-4-amine of��10:1,65.5g, 99%) in a vacuum:1HNMR (400MHz, DMSO-d6) �� 10.52 (bs, 3H), 8.03 (s, 1H); EIMSm/z117 ([M]+)��
Embodiment 2N-(3-chloro-1H-pyrazoles-4-base)-3-((3,3,3-trifluoro propyl) sulfur) propionic acid amide. (compound 2.3):
Hydrochloric acid 3-chloro-1H-pyrazoles-4-amine (5.00g, 32.5mmol), oxolane (25mL) and water (25mL) is injected in 1000-mL, 3-mouth flask. The suspension obtained it is cooled to 5 DEG C and adds sodium bicarbonate (10.9g, 30mmol), then < at 5 DEG C, being added dropwise over 3-((3,3,3-trifluoro propyl) sulfur) propionyl chloride (7.52g, 34.1mmol). React < at 10 DEG C stir 1 hour, this time point thin layer chromatography analysis (ethyl acetate/hexane of eluent: 1:1) shows that initiation material consumes and define desired product. With ethyl acetate (25mL) and water (25mL) diluted reaction mixture. Stratum disjunctum and by ethyl acetate (3 �� 25mL) aqueous layer extracted. Merge organic layer and be concentrated into dry. Residue is suspended in the methyl tertiary butyl ether(MTBE)/heptane (30mL) of 2:1, stirs 1 hour and filters. Methyl tertiary butyl ether(MTBE)/the heptane (20mL) of described solid 2:1 rinses and dry to provide white solid (7.80g, 80%) in a vacuum under room temperature (about 22 DEG C) further: mp83-85 DEG C;1HNMR (400MHz, DMSO-d6) �� 12.90 (s, 1H), 9.59 (s, 1H), 8.02 (s, 1H), 2.82 (t, J=7.2Hz, 2H), 2.76-2.69 (m, 2H), 2.66 (t, J=7.1Hz, 2H), 2.62-2.48 (m, 2H);13CNMR (101MHz, DMSO-d6) �� 168.97,129.95,126.60 (q, J=277.4Hz), 123.42,116.60,35.23,33.45 (q, J=27.3Hz), 26.85,23.03 (q, J=3.4Hz); EIMSm/z301 ([M]+)��
Embodiment 33-((3,3,3-trifluoro propyl) sulfur) propanoic acid:
In 1000-mL, 3-mouth round-bottomed flask, inject 3-bromo-propionic acid (500mg, 3.27mmol) and methanol (10mL), add potassium hydroxide (403mg, 7.19mmol), it is subsequently adding 3,3,3-trifluoro propane-1-sulfur (468mg, 3.60mmol). This mixture heats 4 hours at 50 DEG C, uses the hcl acidifying of 2N afterwards and extracts with methyl tertiary butyl ether(MTBE) (2 �� 10mL). Organic layer is concentrated into dry to provide light yellow oil (580mg, 88%):1HNMR (400MHz, CDCl3) �� 2.83 (td, J=7.1,0.9Hz, 2H), 2.78-2.64 (m, 4H), 2.48-2.32 (m, 2H).
The selectivity synthesis route of 3-((3,3,3-trifluoro propyl) sulfur) propanoic acid:Azodiisobutyronitrile (0.231g is injected in 100mL rustless steel Parr reactor, 1.41mmol), toluene (45mL), 3-mercaptopropionic acid (3.40g, 32.0mmol) and benzene octanone (526.2mg) as interior mark, by nitrogen purge and check pressure. Cool down reactor with dry ice and 3,3,3-trifluoro propenes (3.1g, 32.3mmol) are compressed in reactor. Remove ice bath and reactor be heated to 60 DEG C and stir 27 hours. It is 80% by use benzene octanone, mapping determines inside reactor productivity. Discharge pressure and from reactor, remove crude mixture. By rotary evaporation enriched mixture and the sodium hydroxide adding 50mL10%. This solution is washed, then with the hcl acidifying of 6N to pH��1 with methyl tertiary butyl ether(MTBE) (50mL). With 100mL methyl tertiary butyl ether(MTBE) extraction product, dry over magnesium sulfate, filter and concentrate to obtain the crude title compound (5.34g, 26.4mmol, 83%, the upper 87.5 area % of GC) as oil:1HNMR (400MHz, CDCl3) �� 2.83 (td, J=7.1,0.9Hz, 2H), 2.76-2.64 (m, 4H), 2.47-2.30 (m, 2H);13CNMR (101MHz, CDCl3) �� 177.68,125.91 (q, J=277.1Hz), 34.58 (q, J=28.8Hz), 34.39,26.63,24.09 (q, J=3.3Hz);19FNMR (376MHz, CDCl3)��-66.49��
The selectivity synthesis route of 3-((3,3,3-trifluoro propyl) sulfur) propanoic acid:In tri-mouthfuls of round-bottomed flasks of 250mL, inject toluene (81mL) and be cooled to <-50 DEG C by dry ice/acetone batch. 3,3,3-trifluoro propenes (10.28g, 107.0mmol) are blasted in solvent and remove ice bath. Add 3-mercaptopropionic acid (9.200g, 86.70mmol) and 2,2-dimethoxy-2-phenyl acetophenone (1.070g, 4.170mmol) and open (initial temperature :-24 DEG C) long wavelength's lamp (366nm, 4 watts of UVP lamps). Owing to heating with lamp, reaction reaches the temperature of 27.5 DEG C. This reaction is stirred 4 hours under black light. Close black light after 4 hours and obtain faint yellow oil (line style of 18.09g, 51:1: branched isomer, mark is analyzed as 90wt% line style isomer in GC, and 16.26g is effective, 93%) by rotary evaporation (41 DEG C, 6mmHg) concentration response. Crude starting material it is dissolved in the sodium hydroxide w/w (37.35g) of 10% and washs to remove non polar impurities with toluene (30mL). With hydrochloric acid (2N, 47.81g) by aqueous layer acidified to pH��2-3 and with toluene (50mL) extract. Wash organic layer with water (40mL) and dry over magnesium sulfate, filtering, and concentrate to obtain faint yellow oil (14.15g by rotary evaporation, the line style of 34:1: branched isomer, in GC, mark analyzes the line style isomer for 94wt%, and 13.26g is effective, and 76%).
The selectivity synthesis route of 3-((3,3,3-trifluoro propyl) sulfur) propanoic acid:3-mercaptopropionic acid (3.67g is injected in 100mL rustless steel Parr reactor, 34.6mmol), toluene (30.26g) and 2,2'-azo two (4-methoxyl group-2,4-dimethyl) nitrile (V-70 in penta, 0.543g, 1.76mmol) and by dry ice/acetone batch cool down reactor, by nitrogen purge, and check pressure. Add 3,3,3-trifluoro propenes (3.20g, 33.3mmol) by liquid-transfering gun and allow reaction to be heated to 20 DEG C. After 24 hours, this reaction be heated to 50 DEG C 1 hour to decompose the V-70 initiator of any residual. Allow reaction is cooled to room temperature. By rotary evaporation concentrated solution to provide title compound (6.80g, analyzes the line style isomer for 77.5wt% by mark in GC, and 5.27g is effective, and 76%, GC analyzes the line style for 200:1: branching, and fluorine NMR analyzes the line style for 40:1: branching).
Embodiment 4 methyl-3-((3,3,3-trifluoro propyl) sulfur) propionic ester (compound 7.1):
Azodiisobutyronitrile (0.465g, 2.83mmol), toluene (60mL) and methyl-3-thiopropionate (7.40g, 61.6mmol) is injected, by nitrogen purge and check pressure in 100mL rustless steel Parr reactor. Cool down reactor with dry ice and 3,3,3-trifluoro propenes (5.70g, 59.3mmol) are compressed in reactor. Remove ice bath, reactor is heated to 60 DEG C and stirs 24 hours. Close heating and make reaction keep ambient temperature overnight. From reactor, remove mixture and concentrate as yellow liquid. By vacuum distilling (2Torr, 85 DEG C) distillating liquid and collect three fractions: fraction 1 (1.3g, 6.01mmol, 10%, it is 70.9 area % that GC analyzes), fraction 2 (3.7g, 17.1mmol, 29%, it is 87 area % that GC analyzes), and fraction 3 (4.9g, 22.7mmol, 38%, it is 90.6 area % that GC analyzes):1HNMR (400MHz, CDCl3) �� 3.71 (s, 3H), 2.82, (td, J=7.3,0.7Hz, 2H), 2.75-2.68 (m, 2H), 2.63 (td, J=7.2,0.6Hz, 2H), 2.47-2.31 (m, 2H);13CNMR (101MHz, CDCl3) �� 172.04,125.93 (q, J=277.2Hz), 51.86,34.68 (q, J=28.6Hz), 34.39,27.06,24.11 (q, J=3.3Hz);19FNMR (376MHz, CDCl3)��-66.53��
The selectivity synthesis route of methyl-3-((3,3,3-trifluoro propyl) sulfur) propionic ester:In tri-mouthfuls of round-bottomed flasks of 500mL, inject toluene (200mL) and be cooled to <-50 DEG C by dry ice/acetone batch. Pass the gas through the solvent of cooling by bubbling and 3,3,3-trifluoro propenes (21.8g, 227mmol) are compressed in reaction and remove ice bath. Add methyl-3-thiopropionate (26.8g, 223mmol) He 2,2-dimethoxy-2-phenyl acetophenone (2.72g, 10.61mmol) and opening prevents UVP lamp (4 watts) in 2 centimetres of glass walls to long wave function (366 nanometers). Owing to heating with lamp, reaction reaches the temperature of 35 DEG C. After 4 hours, all of trifluoro propene is consumed or boils out from reaction. Close lamp and reaction is at room temperature stirred overnight. After 22 hours, at room temperature more trifluoro propene (3.1g) bubbling through mixture and is opened light extra 2 hours. Reaction converts 93% so no longer adding trifluoro propene. Close in lamp and rotary evaporator (40 DEG C, 20torr) (line style of 45.7g, 21.3:1: branched isomer, marks in GC and analyzes the pure line style isomer being determined as 75wt% enriched mixture acquisition yellow liquid, 34.3g effectively, productivity in the pot of 71%).
The selectivity synthesis route of methyl-3-((3,3,3-trifluoro propyl) sulfur) propionic ester:Methyl-3-thiopropionate (4.15g is injected in 100mL rustless steel Parr reactor, 34.5mmol), toluene (30.3g) and 2,2'-azo two (4-methoxyl group-2,4-dimethyl) nitrile (V-70 in penta, 0.531g, 1.72mmol) and cool down by dry ice/acetone batch, by nitrogen purge and check pressure. Add 3,3,3-trifluoro propenes (3.40g, 35.4mmol) by liquid-transfering gun and allow reaction to be heated to 20 DEG C. After 23 hours, by reaction be heated to 50 DEG C 1 hour to decompose the V-70 initiator of any residual. Reaction is allowed to be cooled to room temperature. Concentrated solution is to provide title compound (in 7.01g, 66%, GC, mark analyzes the line style isomer for 70.3wt%, and 4.93g is effective, and 66%, GC analyzes the line style for 24:1: branching, and fluorine NMR analyzes the line style for 18:1: branching).
Embodiment 5N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazoles-4-base)-3-((3,3,3-trifluoro propyl) sulfur) propionic acid amide. (compound 5.3):
Hydro-Giene (Water Science). (I) (0.343g is injected in 100mL, 3-mouth round-bottomed flask, 1.80mmol), acetonitrile (50mL), N, N '-dimethyl ethane-1,2-diamidogen (0.318g, 3.61mmol), N-(3-chloro-1H-pyrazoles-4-base)-3-((3,3,3-trifluoro propyl) sulfur) propionic acid amide. (2.72g, 9.02mmol), K2CO3(2.49g, 18.0mol) and 3-bromopyridine (1.71g, 10.8mmol). With nitrogen purge mixture three times and be heated to 80 DEG C 4 hours, this time point thin layer chromatography analysis (eluent: ethyl acetate) shows the remaining starting material of only trace. Pass throughLiner filtering mixt and with acetonitrile (20mL) cleaning pad. Concentrate the filtrate to ethyl acetate/hexane that is dry and that use 0-100% as eluent by flash column chromatography purification residues. The fraction comprising clean product is concentrated into dry and dry to provide white solid (1.82,53%) under vacuo further: mp99-102 DEG C;1HNMR(400MHz,DMSO-d6) �� 9.92 (s, 1H), 9.05 (d, J=2.7Hz, 1H), 8.86 (s, 1H), 8.54 (dd, J=4.5,1.4Hz, 1H), 8.21 (ddd, J=8.4,2.7,1.4Hz, 1H), 7.54 (dd, J=8.4,4.7Hz, 1H), 2.86 (t, J=7.3Hz, 2H), 2.74 (td, J=6.5,5.6,4.2Hz, 4H), 2.59 (ddd, J=11.7,9.7,7.4Hz, 2H);13CNMR(101MHz,DMSO-d6) �� 169.32,147.49,139.44,135.47,133.40,126.60 (q, J=296Hz), 125.49,124.23,122.30,120.00,35.18, (33.42 q, J=27.2Hz), 26.77,23.05 (q, J=3.3Hz); EIMSm/z378 ([M]+)��
Embodiment 6N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazoles-4-base)-N-ethyl-3-((3,3,3-trifluoro propyl) sulfur) propionic acid amide. (compound 6.3):
Cerous carbonate (654mg is injected in 100mL, 3-mouth round-bottomed flask be equipped with mechanical agitator, temperature probe and nitrogen inlet, 2.01mmol), N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazoles-4-base)-3-((3,3,3-trifluoro propyl) sulfur) propionic acid amide. (380mg, 1.00mmol) with DMF (5mL). It is added dropwise over iodoethane (0.0890mL, 1.10mmol). This reaction is stirred 2 hours at 40 DEG C, and now thin layer chromatography analysis (eluent: ethyl acetate) shows the remaining starting material of only trace. Reactant mixture is cooled to 20 DEG C and adds water (20mL). Extract it by ethyl acetate (2 �� 20mL) and the organic layer that merges < is being concentrated into dry at 40 DEG C. The ethyl acetate/hexane using 0-100% passes through flash column chromatography purification residues as eluent. The fraction comprising clean product is concentrated into dry to provide water white oil (270mg, 66%):1HNMR(400MHz,DMSO-d6) �� 9.11 (d, J=2.7Hz, 1H), 8.97 (s, 1H), 8.60 (dd, J=4.8,1.4Hz, 1H), 8.24 (ddd, J=8.4,2.8,1.4Hz, 1H), 7.60 (ddd, J=8.4,4.7,0.8Hz, 1H), 3.62 (q, J=7.1Hz, 2H), 2.75 (t, J=7.0Hz, 2H), 2.66-2.57 (m, 2H), 2.57-2.44 (m, 2H), 2.41 (t, J=7.0Hz, 2H), 1.08 (t, J=7.1Hz, 3H); EIMS:m/z406 ([M]+)��
N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazoles-4-base)-N-ethyl-3-((3,3,3-trifluoro propyl) sulfur) propionyl The selectivity synthesis route of amine (compound 6.3):To 3-mouth round-bottomed flask (50mL) adds sodium hydride (in oil 60%, 0.130g, 3.28mmol) and sulfolane (16mL). Grey suspension stirs 5 minutes, then it was added dropwise over being dissolved in N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazoles-4-the base)-3-((3 of sulfolane (25mL) slowly above at 5 minutes, 3,3-trifluoro propyl) sulfur) propionic acid amide. (1.20g, 3.16mmol). After 3 minutes, mixture becomes beige suspension liquid and allows its stirring 5 minutes, and order adds bromoethane (0.800mL, 10.7mmol) and potassium iodide (0.120g, 0.720mmol) after that time. Then the suspension allowing muddiness at room temperature stirs. By dropwise pouring ammonium formate/acetonitrile solution (30mL) the cancellation reaction of cooling into after 6 hours. Stir the orange cooling solution obtained and add oxolane (40mL). Use benzene octanone as reference material analysis of mixtures, and it was found that containing to have selective 1.09g (85%) desired product relative to retro-Michael type catabolite be 97:3.
Embodiment 7N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazoles-4-base)-N-ethyl-3-((3,3,3-trifluoro propyl) sulfoxide) propionic acid amide. (compound 7.3):
Stirring N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazoles-4-base)-N-ethyl-3-((3 in methanol (180mL), 3,3-trifluoro propyl) sulfur) propionic acid amide. (57.4g, 141mmol). Syringe is used dropwise to add hydrogen peroxide (43.2mL, 423mmol) in the solution obtained. Solution at room temperature stirs 6 hours, and now lcms analysis shows that initial feed consumes. Pour the mixture in dichloromethane (360mL) and wash with aqueous sodium carbonate. Dry organic layer and concentration are to provide deep yellow oil over sodium sulfate. Use the methanol/ethyl acetate eluent raw product of 0-10% by flash column chromatography and merge pure fraction and concentration to provide the expectation product (42.6g, 68%) as oil:1HNMR(400MHz,DMSO-d6) �� 9.09 (dd, J=2.8,0.7Hz, 1H), 8.98 (s, 1H), 8.60 (dd, J=4.7,1.4Hz, 1H), 8.24 (ddd, J=8.4,2.7,1.4Hz, 1H), 7.60 (ddd, J=8.4,4.7,0.8Hz, 1H), 3.61 (q, J=7.4,7.0Hz, 2H), 3.20-2.97 (m, 2H), 2.95-2.78 (m, 2H), 2.76-2.57 (m, 2H), 2.58-2.45 (m, 2H), 1.09 (t, J=7.1Hz, 3H); ESIMSm/z423 ([M+H]+)��
Embodiment 83-((3,3,3-trifluoro propyl) sulfur) propionyl chloride:
The 3-((3 in dichloromethane (3L) is injected in the dry 5L round-bottomed flask be equipped with magnetic stirring apparatus, nitrogen inlet, reflux condenser and thermocouple, 3,3-trifluoro propyl) sulfur) propanoic acid (188g, 883mmol). Then more than 50 minutes, it is added dropwise over thionyl chloride (525g, 321mL, 4.42mol). Reactant mixture is heated to backflow (about 36 DEG C) 2 hours, is then cooled to room temperature. Concentrating under vacuo on the rotary evaporator, distillation (40Torr collects the product of 123-127 DEG C) afterwards is to obtain the title compound (177.3g, 86%) as limpid colourless liquid:1HNMR(400MHz,CDCl3) �� 3.20 (t, J=7.1Hz, 2H), 2.86 (t, J=7.1Hz, 2H), 2.78 2.67 (m, 2H), 2.48 2.31 (m, 2H);19FNMR(376MHz,CDCl3)��-66.42,-66.43,-66.44,-66.44��
Embodiment 93-(((2,2-difluorocyclopropyl) methyl) sulfur) propanoic acid:
At room temperature by powdered potassium hydroxide (423mg, 7.54mmol) with 2-(bromomethyl)-1,1-difluoro cyclopropane (657mg, 3.84mmol) order is added in methanol (2mL) in the solution of the stirring of 3-mercaptopropionic acid (400mg, 3.77mmol). The white suspension obtained stirs 3 hours and with 1N aqueous hydrochloric acid solution cancellation with use diluted ethyl acetate at 65 DEG C. Separate organic facies and by ethyl acetate (2 �� 50mL) aqueous phase extracted. The organic extract merged dries over magnesium sulfate, filters and concentrate in a vacuum to obtain the title molecule (652mg, 84%) as water white oil: IR (KBr thin film) 3025,2927,2665,2569,1696cm-1;1HNMR(400MHz,CDCl3) �� 2.85 (t, J=7.0Hz, 2H), 2.82-2.56 (m, 4H), 1.88-1.72 (m, 1H), 1.53 (dddd, J=12.3,11.2,7.8,4.5Hz, 1H), 1.09 (dtd, J=13.1,7.6,3.7Hz, 1H); ESIMSm/z195.1 ([M-H]-)��
Embodiment 103-(((2,2-difluorocyclopropyl) methyl) sulfur) propionyl chloride:
3L, 3-mouth round-bottomed flask be equipped with overhead, temperature probe and charging hopper and nitrogen inlet under agitation injects the 3-(((2 put at once in dichloromethane (140mL), 2-difluorocyclopropyl) methyl) sulfur) propanoic acid (90.0g, 459mmol). At room temperature, in stirring, it is added dropwise over the thionyl chloride (170mL, 2293mmol) in dichloromethane (100mL). Reactant mixture is heated to 40 DEG C and heats 2 hours. Pass through1HNMR assaying reaction completes (take the reactant mixture measuring consumption, and concentrated by rotary evaporator). Allow reaction to be cooled to room temperature, mixture transferred in dry 3L round-bottomed flask and concentrated by rotary evaporator. This obtains honey color oil (95g). Paper is cleaned by paper gravity filtration content and with Anaesthetie Ether (10mL). Washing liquid is added in flask. This obtains limpid yellow liquid. Liquid is prevented on the rotary evaporator to remove ether. This obtains yellow oil (92.4g). This oil carries out Kugelrohr distillation (bp100-110 DEG C/0.8-0.9mmHg) to provide the title compound (81.4g, 81%) as water white oil:1HNMR(400MHz,CDCl3) �� 3.27 3.12 (m, 2H), 2.89 (t, J=7.1Hz, 2H), 2.67 (ddd, J=6.8,2.6,1.0Hz, 2H), 1.78 (ddq, J=13.0,11.3,7.4Hz, 1H), 1.64 1.46 (m, 1H), 1.09 (dtd, J=13.2,7.7,3.7Hz, 1H).
Biological examples
Embodiment A is to green peach aphid (" GPA ") (the Myzuspersicae) (biological analysis of MYZUPE.
GPA is the most important aphid insect of peach tree, and it causes reducing growth, leaf atrophy and multiple organic death. Itself or dangerous because it act as the bacillicarrier of phytopathogen transport, for instance be under the jurisdiction of Potyvirus Y and the potato leaf curl virus of Solanum/Rhizoma Solani tuber osi race Solanaceae and the multiple mosaic virus of other food pesticide crops many. GPA attacks these plants such as Broccoli, Fructus Arctii, Caulis et Folium Brassicae capitatae, Radix Dauci Sativae, Brassica oleracea L. var. botrytis L., Radix Raphani, Fructus Solani melongenae, Semen phaseoli radiati, Caulis et Folium Lactucae sativae, macadamia, Fructus Caricae, Fructus Piperis, Rhizoma Dioscoreae esculentae, Fructus Lycopersici esculenti, Nasturtium officinale and Fructus Cucurbitae moschatae and other plant. GPA also attacks many ornamental crops, for instance Dianthus carryophyllus, Flos Chrysanthemi, white of blooming Caulis et Folium Brassicae capitatae, poinsettia and Flos Rosae Rugosae. GPA has the toleration to many pesticide developments.
Many molecules disclosed by the invention all use procedures described below test opposing GPA.
In the basin of 3 inches, the Caulis et Folium Brassicae capitatae rice shoot with the little true leaf of 2-3 sheet (3-5cm) of growth is used as test substrate. This rice shoot parasitism 20-5-GPA (without wing adult and nymph stage) one day before chemistry is used. Individually there are four bottles of rice shoot for respective process. Test compound (2mg) is dissolved in 2mL acetone/methanol (1:1) solvent, forms 1000ppm and test the material solution of compound. With the Tween20 in 0.025% water, material solution is diluted 5X and test the solution of compound to obtain 200ppm. Handheld aerosol apparatus is used for the both sides of solution spray to Caulis et Folium Brassicae capitatae leaf until flowing out. With the diluent of only acetone/MeOH (1:1) containing 20% volume, reference plant (solvent inspection) is sprayed. Under about 25 DEG C and envionmental humidity (RH), it is retained in storeroom 3 days before the plant classification processed. Evaluation is that the aphid number lived by counting every plant under the microscope carries out. By the updating formula ((W.S.Abbott of Abbott used as described below, " AMethodofComputingtheEffectivenessofanInsecticide " J.Econ.Entomol18 (1925), pp.265-267) measure control percent.
Correction % comparison=100* (X-Y)/X
Wherein
The quantity of aphid alive on X=solvent inspection plant, and
The quantity of aphid alive on the plant that Y=processes
The form that title is " table 1:GPA (MYZUPE) and sweet potato whitefly-reptile (BEMITA) hierarchical table " shows this result.
The embodiment B biological analysis to sweet potato whitefly reptile (Bemisiatabaci) (BEMITA.)
From the 1800s later stage, sweet potato whitefly Bemisiatabaci (Gennadius) is just documented in the U.S.. The nuisance becoming extremely economy at Florida, Bemisiatabaci in 1986. Aleyrodid is generally with the relatively low surface of the plant leaf blade of they parasitisms for food. In the small reptile stage of egg hatching device, it moves back and forth until it inserts the mouthpart of its small wire draws juice feed will pass through from plant phloem on blade. Adult and nymph excretion honeydew (mainly from the plant sugar of phloem food), the thick liquid of a kind of viscosity, wherein grow fumagine. Jumpbogroup adult and their offspring can cause that rice shoot is dead, or reduce vigor and the productivity of bigger plant, and this is it is usually because siphoned away juice. Velveteen can be sticked together by honeydew, causes that it is difficult to ginning and therefore reduces its value. Fumagine is covering the grown on matrix of honeydew, makes blade dark and gloomy and reduces photosynthesis, and reducing the quality grade of fruit. Its transmission has no effect on the Causative virus of crop culture plant and causes that photosynthesis of plant is disorderly, for instance the irregular maturation of Fructus Lycopersici esculenti and Fructus Cucurbitae moschatae silver color blade are disorderly. Effective insecticide of many pasts is had toleration by aleyrodid.
In the basin of 3 inches, the cotton plant with 1 little (3-5cm) true leaf of growth is used as test material. This kind of plant is placed in the room with adult whitefly. Allow Adult worms producting eggs 2-3 days. After 2-3 days egg-laying seasons, from adult aleyrodid room, take out plant. Hand-held Devilbliss aerosol apparatus (23psi) is used to blow away adult. The plant with ovum group (having 100-300 ovum on each plant) is placed in the storeroom of 82 ��F and 50%RH 5-6 angel's egg hatching and develops into the reptile stage. 4 cotton plants are for respective process. Compound (2mg) is dissolved in the acetone solvent of 1mL, forms the viscous solution of 2000ppm. In this solution with water, the Tween20 of 0.025% dilutes 10 times to obtain the test solution of 200ppm. Hand-held Devilbliss aerosol apparatus is for by spray solution in the both sides of cotton plant leaves until spray to the greatest extent. Only spray reference plant (solvent inspection) with diluent. The plant of classification pre-treatment retains 8-9 days in storeroom under about 82 ��F and 50%RH. It is evaluated by counting the nymph quantity lived on every plant under the microscope. By using Abbott updating formula (referring to above content) test biocidal activity and be listed in table 1.
Table 1:GPA (MYZUPE) and Rhizoma Dioscoreae esculentae white aleyrodid-reptile (BEMITA) table of grading
Embodiment compound BEMITA MYZUPE
1a B B
Compound 2.3 B B
Compound 5.3 B A
Compound 6.3 A A
Compound 7.3 A A
Comparative example
Example CE-1N-(1-acetyl group-1H-pyrazoles-4-base) acetamide:
1H-pyrazoles-4-amine (5g, 60.2mmol) and dichloromethane (50mL) is injected in the 3-mouth flask of 250-mL. The suspension obtained is cooled to 5 DEG C and adds triethylamine (9.13g, 90.0mmol), then < is adding acetic anhydride (7.37g, 72.2mmol) at 20 DEG C. Reaction is stirring 18 hours at room temperature, and this time point thin layer chromatography analysis (eluent: ethyl acetate) shows that reaction is not fully complete. Add extra triethylamine (4.57g, 45.0mmol) and acetic anhydride (3.70g, 36.0mmol) and react at 30 DEG C, heat extra 3 hours to obtain dark solution, this time point thin layer chromatography analysis shows the remaining starting material of only trace. Use ethyl acetate eluent by flash column chromatography purification reaction mixture. Merge the fraction comprising clean product and be concentrated into dry to provide pale solid. This solid is at room temperature dry 18 hours (5.55g, 55%) in a vacuum:1HNMR(400MHz,DMSO-d6) �� 10.30 (s, 1H), 8.39 (d, J=0.7Hz, 1H), 7.83 (d, J=0.7Hz, 1H), 2.60 (s, 3H), 2.03 (s, 3H); EIMSm/z167 ([M]+)��
Example CE-2N-(3-bromo-1H-pyrazoles-4-base) acetamide:
1H-pyrazoles-4-amine hydrobromate (4.00g, 24.7mmol) and water (23mL) is injected in the 3-mouth round-bottomed flask of 250-mL. In 10 minutes, in mixture, it is slowly added sodium bicarbonate (8.30g, 99.0mmol), is subsequently adding oxolane (23mL). Mixture is cooled to 5 DEG C and in 30 minutes add acetic anhydride (2.60g, 25.4mmol) be maintained with internal temperature < 10 DEG C. Reactant mixture stirs 20 minutes at��5 DEG C, now1The bright initiation material of HNMR and UPLC analytical table has consumed and has defined the by-product of desired product and diacetyl. It is extracted with ethyl acetate reaction, dries organic layer over magnesium sulfate and concentrate. Crude mixture is ground to remove the by-product of diacetyl to provide��1.24g white solid with methyl tertiary butyl ether(MTBE).1HNMR analyzes display, and it is the desired of 1:1.1 and less desirable diacetyl product. Ethyl acetate/the acetone using 50-100% passes through flash column chromatography pure solid to provide the product (��800mg) as the expectation product (380mg, 7.5%) of white solid and the diacetyl as white solid as eluent:1HNMR(400MHz,DMSO-d6) �� 13.01 (s, 1H), 9.36 (s, 1H), 7.92 (s, 1H), 2.03 (s, 3H);13CNMR (101MHz, DMSO) �� 167.94,123.93,119.19,119.11,22.63; ESIMSm/z204 ([M+H]+)��
The alkylation that example CE-3 decomposes relative to retro-Michael type:
Sodium hydride (in oil 60%, 1.03eq) and solvent (1vol) stir 5 minutes. N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazoles-4-the base)-3-((3 being dissolved in solvent (2vol) it is slowly added dropwise in 5 minutes, 3,3-trifluoro propyl) sulfur)-propionic acid amide. (1eq). Order adds bromoethane (3.3eq) and additive (0.22eq). Then suspension is allowed at room temperature to stir until observing that initiation material consumes. The compound 6.3 selectivity (referring to table 2) to catabolite is measured by HPLC.
Table 2
Although should be understood that the present invention is described by the particular embodiment set up in detail, but these embodiments exist in the way of rule of the present invention explanation, and the present invention is not necessarily limited to this. Some on any raw material, method step or chemical equation provided is improved and deformation will be apparent from for a person skilled in the art, it is without departing from the true spirit of the present invention and scope, and all these improve and deformation will be regarded as in the scope of claims below.

Claims (17)

1. a preparation method for insecticidal thioethers (3a), described insecticidal thioethers (3a) can be used in insecticidal thioethers (3b), (3c) and parasite killing sulfoxide (3d) preparation,
Wherein:
R1Selected from C1-C4Haloalkyl and C1-C4Alkyl-C3-C6Halogenated cycloalkyl,
It includes making 3-chloro-1H-pyrazoles-4-amine hydrochlorate
With activated carbonyl thioether X1C (=O) C1-C4-alkyl-S-R1Reaction, wherein X1Selected from Cl, OC (=O) C1-C4The group of alkyl or formation activating carboxy acid.
2. a preparation method for insecticidal thioethers (3b), described insecticidal thioethers (3b) can be used for insecticidal thioethers (3c) and the preparation of parasite killing sulfoxide (3d):
Wherein R1Selected from C1-C4Haloalkyl and C1-C4Alkyl-C3-C6Halogenated cycloalkyl,
It includes thioether (3a)
With haloperidid heteraryl under the existence of mantoquita, amine and alkali.
3. a preparation method for thioether (3c), described thioether (3c) is as insecticide and can be used for the preparation of parasite killing sulfoxide (3d):
Wherein R1Selected from C1-C4Haloalkyl and C1-C4Alkyl-C3-C6Halogenated cycloalkyl and R2Selected from C1-C4-alkyl and C2-C4-alkynyl,
It includes thioether (3b)
With R2-X2Alkylation in the presence of base, wherein X2It it is leaving group.
4. method according to claim 3, wherein R2-X2It it is iodoethane.
5. a method, comprising:
A () uses concentrated hydrochloric acid at the palladium aluminium oxide of the temperature triethyl silicane of about 1 to about 4 equivalent of about 10 DEG C to about 20 DEG C and about 1wt% to 10wt% by 4-nitropyrazole
Halogenation and reduction,
To obtain 3-chloro-1H-pyrazoles-4-amine hydrochlorate (1a)
B () makes (1a) and activated carbonyl thioether X1C (=O) C1-C4-alkyl-S-R1Reaction, wherein X1Selected from Cl, OC (=O) C1-C4The group of alkyl or formation activating carboxy acid, and R1Selected from C1-C4Haloalkyl and C1-C4Alkyl-C3-C6Halogenated cycloalkyl, to obtain thioether
C () is used under the existence of mantoquita, amine and alkali with haloperidid to (3a) heteraryl to obtain thioether (3b)
D () uses R in the presence of base2-X2To thioether (3b) alkylation, to obtain thioether (3c), wherein R2Selected from C1-C4-alkyl and C2-C4-alkynyl, and wherein X2It is leaving group,
6. the method any one of claim 1,2,3 or 5, wherein R1It is C1-C4Haloalkyl.
7. the method any one of claim 1,2,3 or 5, wherein R1It is CH2CH2CF3��
8. the method any one of claim 1,2,3 or 5, wherein R1It is C1-C4Alkyl-C3-C6Halogenated cycloalkyl.
9. the method any one of claim 1,2,3 or 5, wherein R1It is CH2(2,2-difluorocyclopropyl).
10. compound N-(3-chloro-1H-pyrazoles-4-base)-3-((3,3,3, trifluoro propyl) sulfur) propionic acid amide. (compound 2.3)
11. a method, it includes N-(3-chloro-1H-pyrazoles-4-base)-3-((3,3,3, trifluoro propyl) sulfur) propionic acid amide. (compound 2.3)
It is applied to location to control the insecticide perched in described location.
12. method according to claim 1, wherein R1It is CH2CH2CF3, and described activated carbonyl thioether X1C (=O) C1-C4-alkyl-S-R1Prepared by following formula material, wherein X1Selected from Cl, OC (=O) C1-C4The group of alkyl or formation activating carboxy acid,
Described material is prepared by 3-mercaptopropionic acid and ester thereof and the photochemistry free radical coupling in inert organic solvents under 2,2-dimethoxy-2-phenyl acetophenone initiator and long wavelength ultraviolet light exist of 3,3,3-trifluoro propene.
13. method according to claim 5, wherein R1It is CH2CH2CF3, and described activated carbonyl thioether X1C (=O) C1-C4-alkyl-S-R1Prepared by following formula material, wherein X1Selected from Cl, OC (=O) C1-C4The group of alkyl or formation activating carboxy acid,
Described material is prepared by 3-mercaptopropionic acid and ester thereof and the photochemistry free radical coupling in inert organic solvents under 2,2-dimethoxy-2-phenyl acetophenone initiator and long wavelength ultraviolet light exist of 3,3,3-trifluoro propene.
14. method according to claim 1, wherein R1It is CH2CH2CF3, and described activated carbonyl thioether X1C (=O) C1-C4-alkyl-S-R1Prepared by following formula material, wherein X1Selected from Cl, OC (=O) C1-C4The group of alkyl or formation activating carboxy acid,
Described material passes through 3-mercaptopropionic acid and 3,3,3-trifluoro propene is 2, prepared by the coupling carrying out low temperature free radical initiation under the existence of nitrile (V-70) initiator at the temperature of about-50 DEG C to about 40 DEG C in inert organic solvents in 2'-azo two (4-methoxyl group-2,4-dimethyl) penta.
15. method according to claim 5, wherein R1It is CH2CH2CF3, and described activated carbonyl thioether X1C (=O) C1-C4-alkyl-S-R1Prepared by following formula material, wherein X1Selected from Cl, OC (=O) C1-C4The group of alkyl or formation activating carboxy acid,
Described material passes through 3-mercaptopropionic acid and 3,3,3-trifluoro propene is 2, prepared by the coupling carrying out low temperature free radical initiation under the existence of nitrile (V-70) initiator at the temperature of about-50 DEG C to about 40 DEG C in inert organic solvents in 2'-azo two (4-methoxyl group-2,4-dimethyl) penta.
16. the method according to claim 3 or 4, wherein alkylation carries out under the existence of polar non-solute and under the existence of iodide additive.
17. method according to claim 5, wherein thioether (3c)
By in the presence of base, use R under the existence of polar non-solute and under the existence of iodide additive2-X2Prepared by thioether (3b) alkylation
Wherein R2Selected from C1-C4-alkyl and C2-C4-alkynyl, wherein X2It it is leaving group.
CN201480057195.1A 2013-10-17 2014-10-17 The method for preparing Pesticidal compound Expired - Fee Related CN105636446B (en)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US201361892124P 2013-10-17 2013-10-17
US61/892,124 2013-10-17
US201462001925P 2014-05-22 2014-05-22
US62/001,925 2014-05-22
US201462034456P 2014-08-07 2014-08-07
US62/034,456 2014-08-07
PCT/US2014/061014 WO2015058023A1 (en) 2013-10-17 2014-10-17 Processes for the preparation of pesticidal compounds

Publications (2)

Publication Number Publication Date
CN105636446A true CN105636446A (en) 2016-06-01
CN105636446B CN105636446B (en) 2018-07-13

Family

ID=52826738

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201480057195.1A Expired - Fee Related CN105636446B (en) 2013-10-17 2014-10-17 The method for preparing Pesticidal compound

Country Status (9)

Country Link
US (5) US9085564B2 (en)
EP (1) EP3057428A4 (en)
JP (1) JP2016535008A (en)
KR (1) KR20160074542A (en)
CN (1) CN105636446B (en)
CA (1) CA2925952A1 (en)
IL (1) IL245066A0 (en)
MX (1) MX2016004946A (en)
WO (1) WO2015058023A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110325036A (en) * 2016-12-29 2019-10-11 美国陶氏益农公司 The method for being used to prepare Pesticidal compound

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2925954A1 (en) 2013-10-17 2015-04-23 Dow Agrosciences Llc Processes for the preparation of pesticidal compounds
EP3057425A4 (en) 2013-10-17 2017-08-02 Dow AgroSciences LLC Processes for the preparation of pesticidal compounds
CA2926095A1 (en) 2013-10-17 2015-04-23 Dow Agrosciences Llc Processes for the preparation of pesticidal compounds
CN105636441B (en) 2013-10-17 2018-06-15 美国陶氏益农公司 The method for preparing Pesticidal compound
WO2015058022A1 (en) * 2013-10-17 2015-04-23 Dow Agrosciences Llc Processes for the preparation of pesticidal compounds
CN105636446B (en) 2013-10-17 2018-07-13 美国陶氏益农公司 The method for preparing Pesticidal compound
WO2015058021A1 (en) 2013-10-17 2015-04-23 Dow Agrosciences Llc Processes for the preparation of pesticidal compounds
SE1400492A1 (en) 2014-01-22 2015-07-23 Climeon Ab An improved thermodynamic cycle operating at low pressure using a radial turbine
WO2016018444A1 (en) 2014-07-31 2016-02-04 Dow Agrosciences Llc Process for the preparation of 3-(3-chloro-1h-pyrazol-1-yl)pyridine
AR098110A1 (en) 2014-07-31 2016-05-04 Dow Agrosciences Llc PROCESS FOR THE PREPARATION OF 3- (3-CHLORINE-1H-PIRAZOL-1-IL) PIRIDINE
CA2954345A1 (en) 2014-07-31 2016-02-04 Dow Agrosciences Llc Process for the preparation of 3-(3-chloro-1h-pyrazol-1-yl)pyridine
CA2958058A1 (en) 2014-08-19 2016-02-25 Dow Agrosciences Llc Process for the preparation of 3-(3-chloro-1h-pyrazol-1-yl)pyridine
BR112017004613A2 (en) 2014-09-12 2017-12-05 Dow Agrosciences Llc Process for the preparation of 3- (3-chloro-1h-pyrazol-1-yl) pyridine
US10100033B2 (en) 2016-12-29 2018-10-16 Dow Agrosciences Llc Processes for the preparation of pesticidal compounds
TW201823201A (en) * 2016-12-29 2018-07-01 美商陶氏農業科學公司 Processes for the preparation of pesticidal compounds
IL278766B2 (en) 2018-06-08 2023-11-01 Corteva Agriscience Llc Molecule, n-(3-chloro-1-(pyridin-3-yl)-1h-pyrazol-4-yl)-2- (methylsulfonyl)propanamide, having pesticidal utility
EP4281440A1 (en) * 2021-01-21 2023-11-29 Corteva Agriscience LLC Processes related to formation of n-(3-chloro-1-(pyridin-3-yl)-1h-pyrazol-4-yl)-2-(methylsulfonyl)propanamide

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1373662A (en) * 1999-08-12 2002-10-09 法玛西雅意大利公司 3(5)-amino-pyrazole derivs., process for their preparation and their use as antitumor agents
WO2012061290A2 (en) * 2010-11-03 2012-05-10 Dow Agrosciences Llc Pesticidal compositions and processes related thereto

Family Cites Families (172)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3597341A (en) * 1968-09-11 1971-08-03 Exxon Research Engineering Co Selective addition of thiols to allylic isocyanates and isothiocyanates
CA962269A (en) 1971-05-05 1975-02-04 Robert E. Grahame (Jr.) Thiazoles, and their use as insecticides
US4556671A (en) 1979-07-13 1985-12-03 Burroughs Wellcome Co. Pharmaceutical formulations
US4407803A (en) 1981-08-17 1983-10-04 Abbott Laboratories Antiinflammatory 1-(quinolinyl)-2-pyrazoline derivatives
FR2517176A1 (en) 1981-12-01 1983-06-03 Rhone Poulenc Agrochimie INSECTICIDE AND ACARICIDE ASSOCIATION OF PYRETHROID
US4528291A (en) 1982-06-22 1985-07-09 Schering Corporation 2-(4'-Pyridinyl)-thiazole compounds and their use in increasing cardiac contractility
US4824953A (en) 1983-11-15 1989-04-25 Riker Laboratories, Inc. Multi-step process for producing 5-hydroxy-N-(6-oxo-piperidyl-methyl)-2-(2,2,2-trifluoro-ethoxy)-benzamide and derivatives
EP0178035B1 (en) 1984-05-12 1990-01-03 FISONS plc Anti-inflammatory 1,n-diarylpyrazol-3-amines, compositions containing them and processes for their preparation
IT1183181B (en) 1985-02-07 1987-10-05 Corvi Camillo Spa DERIVATIVES OF 3-METHYL-IMIDAZO (4,5-C) PIRAZOLE WITH THERAPEUTIC ACTIVITY AND PROCEDURE FOR THEIR PREPARATION
DE3520328A1 (en) 1985-06-07 1986-12-11 Bayer Ag, 5090 Leverkusen 5-AMINO-4-HETEROCYCLYL-1-PYRIDYL-PYRAZOLE
GB8625897D0 (en) 1986-10-29 1986-12-03 Ici Plc Insecticidal thioethers derivatives
JPS62153273A (en) 1985-12-26 1987-07-08 Tokuyama Soda Co Ltd Pyrazole compound
DE3600950A1 (en) 1986-01-15 1987-07-16 Bayer Ag 5-ACYLAMIDO-1-ARYL-PYRAZOLE
JPS62153273U (en) 1986-03-19 1987-09-29
DE3618717A1 (en) 1986-06-04 1987-12-10 Bayer Ag 5- ACYLAMINO-PYRAZOLE DERIVATIVES
JPH07106964B2 (en) 1987-01-14 1995-11-15 株式会社トクヤマ Fruit picking agent
US5599944A (en) 1987-03-24 1997-02-04 Bayer Aktiengesellschaft Intermediates for herbicidal sulphonylaminocarbonyltriazolinones having substituents which are bonded via sulphur
DE3936622A1 (en) 1989-11-03 1991-05-08 Bayer Ag HALOGENED SULFONYLAMINOCARBONYLTRIAZOLINONE
JPS63174905U (en) 1987-04-23 1988-11-14
JPH089541B2 (en) 1988-03-07 1996-01-31 三井東圧化学株式会社 Brain edema inhibitor containing pyrazoles as the main component
US5300480A (en) 1989-04-13 1994-04-05 Bayer Aktiengesellschaft Herbicidal sulphonylaminocarbonyltriazolinones having two substituents bonded via oxygen
US5541337A (en) 1989-04-13 1996-07-30 Bayer Aktiengesellschaft Substituted 5-alkoxy-1,2,4-triazol-3-(thi)ones
US5241074A (en) 1988-05-09 1993-08-31 Bayer Aktiengesellschaft Sulphonylaminocarbonyltriazolinones
US5220028A (en) 1988-10-27 1993-06-15 Nissan Chemical Industries, Ltd. Halogeno-4-methylpyrazoles
US5534486A (en) 1991-04-04 1996-07-09 Bayer Aktiengesellschaft Herbicidal sulphonylaminocarbonyl triazolinones having substituents bonded via oxygen
US5366987A (en) 1991-08-22 1994-11-22 Warner-Lambert Company Isoxazolyl-substituted alkyl amide ACAT inhibitors
TW336932B (en) 1992-12-17 1998-07-21 Pfizer Amino-substituted pyrazoles
WO1997015567A1 (en) 1995-10-20 1997-05-01 Dr. Karl Thomae Gmbh 5-membered heterocycles, pharmaceutical agents containing said compounds and the use thereof and methods of producing them
US5854265A (en) 1996-04-03 1998-12-29 Merck & Co., Inc. Biheteroaryl inhibitors of farnesyl-protein transferase
EP0891356A1 (en) 1996-04-03 1999-01-20 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
TW430660B (en) 1996-05-30 2001-04-21 Mochida Pharm Co Ltd Novel benzindole derivatives for neuron cell protection, processes for production, and the pharmaceutical compounds containing them
US5854264A (en) 1996-07-24 1998-12-29 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
WO1998049166A1 (en) 1997-04-25 1998-11-05 Pfizer Limited PYRAZOLOPYRIMIDINONES WHICH INHIBIT TYPE 5 CYCLIC GUANOSINE 3',5'-MONOPHOSPHATE PHOSPHODIESTERASE (cGMP PDE5) FOR THE TREATMENT OF SEXUAL DYSFUNCTION
DE19725450A1 (en) 1997-06-16 1998-12-17 Hoechst Schering Agrevo Gmbh 4-Haloalkyl-3-heterocyclylpyridines and 4-haloalkyl-5-heterocyclylpyrimidines, processes for their preparation, compositions containing them and their use as pesticides
JP4136041B2 (en) 1997-12-04 2008-08-20 日立建機株式会社 Hydraulic drive device for hydraulic working machine
US6271237B1 (en) 1997-12-22 2001-08-07 Dupont Pharmaceuticals Company Nitrogen containing heteromatics with ortho-substituted P1s as factor Xa inhabitors
CA2332957A1 (en) 1998-06-05 1999-12-09 Boehringer Ingelheim Pharmaceuticals, Inc. Substituted 1-(4-aminophenyl)pyrazoles and their use as anti-inflammatory agents
GB9827882D0 (en) 1998-12-17 1999-02-10 Smithkline Beecham Plc Novel compounds
FR2789076B1 (en) 1999-02-02 2001-03-02 Synthelabo ALPHA-AZACYCLOMETHYL QUINOLEINE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION
FR2789387B1 (en) 1999-02-04 2001-09-14 Aventis Cropscience Sa NEW PROCESS FOR THE PREPARATION OF PESTICIDE INTERMEDIATES
CA2382676A1 (en) 1999-11-05 2001-05-17 Warner-Lambert Company Prevention of plaque rupture by acat inhibitors
EP1256569B1 (en) 2000-02-16 2010-07-07 Ishihara Sangyo Kaisha, Ltd. Phenacylamine derivatives, production thereof and pest controllers containing the derivatives
GB0011095D0 (en) 2000-05-08 2000-06-28 Black James Foundation astrin and cholecystokinin receptor ligands (III)
US6645990B2 (en) 2000-08-15 2003-11-11 Amgen Inc. Thiazolyl urea compounds and methods of uses
WO2002023986A1 (en) 2000-08-25 2002-03-28 Sankyo Company, Limited 4-acylaminopyrazole derivatives
AU2001290258A1 (en) * 2000-09-22 2002-04-02 Nihon Nohyaku Co. Ltd. N-(4-pyrazolyl)amide derivatives, chemicals for agricultural and horticultural use, and usage of the same
JP2003012651A (en) * 2000-09-22 2003-01-15 Nippon Nohyaku Co Ltd N-(4-pyrazolyl)amide derivative, agricultural and horticultural agent and use thereof
US20020134012A1 (en) 2001-03-21 2002-09-26 Monsanto Technology, L.L.C. Method of controlling the release of agricultural active ingredients from treated plant seeds
CN100540538C (en) 2001-04-16 2009-09-16 田边三菱制药株式会社 The high conductance calcium-activated k channel is opened agent
EP1256578B1 (en) 2001-05-11 2006-01-11 Pfizer Products Inc. Thiazole derivatives and their use as cdk inhibitors
ATE298749T1 (en) 2001-07-05 2005-07-15 Pfizer Prod Inc HETEROCYCLO-ALKYLSULFONYL PYRAZOLES AS ANTI-INFLAMMATORY/ANALGESIC AGENTS
FR2827603B1 (en) 2001-07-18 2003-10-17 Oreal COMPOUNDS DERIVED FROM DIAMINOPYRAZOLE SUBSTITUTED BY A HETEROAROMATIC RADICAL AND THEIR USE IN OXIDATION DYES OF KERATINIC FIBERS
TWI356822B (en) 2001-08-13 2012-01-21 Du Pont Novel substituted dihydro 3-halo-1h-pyrazole-5-car
GB0123589D0 (en) 2001-10-01 2001-11-21 Syngenta Participations Ag Organic compounds
US7192906B2 (en) 2001-12-20 2007-03-20 Sds Biotech K.K. Substituted pyrazole derivatives, production process thereof, and herbicide compositions containing the derivatives
DE60221627D1 (en) 2001-12-21 2007-09-20 Virochem Pharma Inc Thiazole derivatives and their use for the treatment or prevention of infections by flaviviruses
US6878196B2 (en) 2002-01-15 2005-04-12 Fuji Photo Film Co., Ltd. Ink, ink jet recording method and azo compound
JP2003212864A (en) 2002-01-24 2003-07-30 Sankyo Co Ltd 5-(m-cyanobenzylamino)thiazole derivative
DE60324898D1 (en) 2002-02-25 2009-01-08 Lilly Co Eli MODULATORS OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS
JP2004051628A (en) 2002-05-28 2004-02-19 Ishihara Sangyo Kaisha Ltd Pyridine-based compound or its salt, method for producing the same, and herbicide containing the same
AU2003254053A1 (en) 2002-07-23 2004-02-09 Smithkline Beecham Corporation Pyrazolopyrimidines as protein kinase inhibitors
US6737382B1 (en) 2002-10-23 2004-05-18 Nippon Soda Co. Ltd. Insecticidal aminothiazole derivatives
CA2504320A1 (en) 2002-10-30 2004-05-21 Vertex Pharmaceuticals Incorporated Compositions useful as inhibitors of rock and other protein kinases
ES2436746T3 (en) 2002-12-03 2014-01-07 Merial Limited Pesticide derivatives of 5- (acylamino) pyrazole
US7429581B2 (en) 2002-12-23 2008-09-30 Sanofi-Aventis Deutschland Gmbh Pyrazole-derivatives as factor Xa inhibitors
JP4397615B2 (en) 2003-03-27 2010-01-13 富士フイルム株式会社 Inkjet ink and ink set
GB0312654D0 (en) 2003-06-03 2003-07-09 Glaxo Group Ltd Therapeutically useful compounds
WO2005028410A1 (en) 2003-09-19 2005-03-31 Ube Industries, Ltd. Method for producing nitrile compound, carboxylic acid compound or carboxylate compound
CN100432038C (en) 2003-09-19 2008-11-12 宇部兴产株式会社 Method for producing nitrile compound, carboxylic acid compound or carboxylate compound
US7514464B2 (en) 2003-12-18 2009-04-07 Pfizer Limited Substituted arylpyrazoles
DE102004003812A1 (en) 2004-01-25 2005-08-11 Aventis Pharma Deutschland Gmbh Aryl-substituted heterocycles, methods of their preparation and their use as pharmaceuticals
US7319108B2 (en) 2004-01-25 2008-01-15 Sanofi-Aventis Deutschland Gmbh Aryl-substituted heterocycles, process for their preparation and their use as medicaments
US7297168B2 (en) 2004-02-02 2007-11-20 The Procter & Gamble Company Keratin dyeing compounds, keratin dyeing compositions containing them, and use thereof
AU2005223483B2 (en) 2004-03-18 2009-04-23 Zoetis Llc N-(1-arylpyrazol-4l)sulfonamides and their use as parasiticides
US20070167426A1 (en) 2004-06-02 2007-07-19 Schering Corporation Compounds for the treatment of inflammatory disorders and microbial diseases
GT200500179A (en) 2004-07-01 2006-02-23 SYNERGIST MIXTURES OF ANTRANILAMIDE AGENTS FOR THE CONTROL OF INVERTEBRATE PESTS
MX2007002274A (en) 2004-08-23 2007-05-07 Lilly Co Eli Histamine h3 receptor agents, preparation and therapeutic uses.
EP1794156A2 (en) 2004-09-23 2007-06-13 Pfizer Products Incorporated Trombopoietin receptor agonists
US7923573B2 (en) 2004-10-27 2011-04-12 Daiichi Sankyo Company, Limited Benzene compound having 2 or more substituents
EP2942349A1 (en) 2004-12-23 2015-11-11 Deciphera Pharmaceuticals, LLC Enzyme modulators and treatments
CA2593439C (en) 2005-01-14 2014-02-25 F. Hoffmann-La Roche Ag Thiazole-4-carboxamide derivatives as mglur5 antagonists
US7790720B2 (en) 2005-03-31 2010-09-07 Ucb Pharma, S.A. Compounds comprising an oxazole or thiazole moiety, processes for making them, and their uses
BRPI0611798A2 (en) * 2005-06-15 2009-01-13 Pfizer Ltd substituted arylpyrazole compounds, their pharmaceutical composition and use
US7608592B2 (en) 2005-06-30 2009-10-27 Virobay, Inc. HCV inhibitors
KR100654328B1 (en) 2005-08-26 2006-12-08 한국과학기술연구원 Piperazynylalkylpyrazole devrivatives useful as selective t-type calcium channel blockers and preparation method thereof
BRPI0706610A2 (en) 2006-01-18 2011-04-05 Siena Biotech Spa nicotinically acetylcholine alpha 7 receptor modulators and therapeutic uses of these
JP2009524677A (en) 2006-01-25 2009-07-02 シンタ ファーマシューティカルズ コーポレーション Thiazole and thiadiazole compounds for inflammation and immune related use
EP2038272B8 (en) 2006-06-30 2013-10-23 Sunesis Pharmaceuticals, Inc. Pyridinonyl pdk1 inhibitors
US20090325956A1 (en) 2006-10-13 2009-12-31 Takahiko Taniguchi Aromatic amine derivative and use thereof
JO2754B1 (en) 2006-12-21 2014-03-15 استرازينكا ايه بي Indazolyl amide derivatives for the treatment of glucocorticoid receptor mediated disorders
US7795249B2 (en) 2006-12-22 2010-09-14 Millennium Pharmaceuticals, Inc. Certain pyrazoline derivatives with kinase inhibitory activity
GB0701426D0 (en) 2007-01-25 2007-03-07 Univ Sheffield Compounds and their use
US20090069288A1 (en) 2007-07-16 2009-03-12 Breinlinger Eric C Novel therapeutic compounds
EP2173728A2 (en) 2007-07-17 2010-04-14 Amgen Inc. Heterocyclic modulators of pkb
AU2008277783B2 (en) 2007-07-17 2012-09-20 F. Hoffmann-La Roche Ag Inhibitors of 11beta-hydroxysteroid dehydrogenase
US8293919B2 (en) 2007-07-23 2012-10-23 Crestone, Inc. Antibacterial sulfone and sulfoxide substituted heterocyclic urea compounds
CN101918389A (en) 2007-11-02 2010-12-15 梅特希尔基因公司 Histone deacetylase inhibitor
US8389567B2 (en) 2007-12-12 2013-03-05 Calcimedica, Inc. Compounds that modulate intracellular calcium
MX339122B (en) 2008-02-12 2016-05-12 Dow Agrosciences Llc Pesticidal compositions.
CN101945905B (en) 2008-02-15 2013-06-26 旭化成电子材料株式会社 Resin composition
CA2719847A1 (en) 2008-04-21 2010-01-28 Merck Sharp & Dohme Corp. Inhibitors of janus kinases
BRPI0915350A2 (en) 2008-06-13 2016-05-03 Bayer Cropscience Ag new heteroatomic amides and thioamides as pesticides
TW201004941A (en) 2008-07-16 2010-02-01 Wyeth Corp Alpha7 nicotinic acetylcholine receptor inhibitors
ES2567183T3 (en) 2008-07-17 2016-04-20 Bayer Cropscience Ag Heterocyclic compounds such as pesticides
JP2010030970A (en) 2008-07-31 2010-02-12 Bayer Cropscience Ag Insecticidal benzenedicarboxamide derivative
WO2010032874A1 (en) 2008-09-19 2010-03-25 住友化学株式会社 Composition for agricultural use
CA2737437A1 (en) 2008-09-19 2010-03-25 Absolute Science, Inc. Methods of treating a botulinum toxin related condition in a subject
GB0817617D0 (en) 2008-09-25 2008-11-05 Ricardo Uk Ltd Bearing for wind turbine
CN102186825A (en) 2008-10-21 2011-09-14 麦它波莱克斯股份有限公司 Aryl gpr120 receptor agonists and uses thereof
CN101747276B (en) 2008-11-28 2011-09-07 中国中化股份有限公司 Ether compound with nitrogenous quinary alloy and application thereof
CN102264737A (en) 2008-12-23 2011-11-30 雅培制药有限公司 Anti-viral compounds
JP5894438B2 (en) 2009-02-11 2016-03-30 ダウ アグロサイエンシィズ エルエルシー Insecticidal composition
US8785468B2 (en) 2009-02-13 2014-07-22 Amgen Inc. Phenylalanine amide derivatives useful for treating insulin-related diseases and conditions
UA107791C2 (en) 2009-05-05 2015-02-25 Dow Agrosciences Llc Pesticidal compositions
BRPI1010909A2 (en) 2009-05-19 2015-09-08 Bayer Cropscience Ag "arylpyrroline insecticide"
FI20095678A0 (en) 2009-06-16 2009-06-16 Biotie Therapies Oy Urea substituted sulfonamide derivatives
UA110324C2 (en) 2009-07-02 2015-12-25 Genentech Inc Jak inhibitory compounds based on pyrazolo pyrimidine
CN102471252B (en) 2009-08-10 2014-07-02 住友化学株式会社 Process for preparation of (fluoroalkylthio)acetic acid esters
JP2012254939A (en) 2009-10-07 2012-12-27 Astellas Pharma Inc Oxazole compound
MX2012003376A (en) 2009-10-12 2012-06-27 Bayer Cropscience Ag Amides and thioamides as pesticides.
BR112012006956A2 (en) 2009-10-12 2015-09-15 Bayer Cropscience Ag 1- (pyrida-3-yl) pyrazolol and 1- (pyrimide-5-yl) pyrazolol as pesticides
US8883785B2 (en) 2010-01-25 2014-11-11 Chdi Foundation, Inc. Certain kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof
EP2539330B1 (en) 2010-02-22 2016-11-09 Syngenta Participations AG Dihydrofuran derivatives as insecticidal compounds
CN104940200B (en) 2010-03-30 2019-06-28 维颂公司 Inhibitor of the polysubstituted aromatic compounds as fibrin ferment
JP5826822B2 (en) 2010-04-16 2015-12-02 バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＢａｙｅｒ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ ＧｍｂＨ Novel heterocyclic compounds as pest control agents
EP2382865A1 (en) 2010-04-28 2011-11-02 Bayer CropScience AG Synergistic active agent compounds
CN102971315B (en) 2010-05-05 2015-07-22 拜耳知识产权有限责任公司 Thiazol derivatives as pest control agents
EP2585467B1 (en) 2010-06-24 2016-03-02 Gilead Sciences, Inc. Pyrazolo[1,5-a]pyrimidines and -triazines as antiviral agents
BR112012033411A2 (en) 2010-06-28 2015-09-15 Bayer Ip Gmbh heterocyclic compounds as pesticides
US20130109682A1 (en) 2010-07-06 2013-05-02 Novartis Ag Cyclic ether compounds useful as kinase inhibitors
EP2593447B1 (en) 2010-07-15 2016-08-17 Bayer Intellectual Property GmbH 3-pyridyl-heteroarylcarboxamide compounds as pesticides
CA2808234A1 (en) 2010-08-31 2012-03-08 Dow Agrosciences Llc Pesticidal compositions
JP2012082186A (en) 2010-09-15 2012-04-26 Bayer Cropscience Ag Insecticidal arylpyrrolidines
JP5953308B2 (en) 2010-10-22 2016-07-20 バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＢａｙｅｒ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ ＧｍｂＨ New heterocyclic compounds as pesticides
CN103281901B (en) 2010-11-03 2016-12-28 陶氏益农公司 Pesticidal combination and relative method
WO2012070114A1 (en) 2010-11-24 2012-05-31 塩野義製薬株式会社 Sulfamide derivative having npy y5 receptor antagonism
JPWO2012102387A1 (en) 2011-01-27 2014-07-03 日産化学工業株式会社 Pyrazole derivatives and pest control agents
JPWO2012108511A1 (en) 2011-02-09 2014-07-03 日産化学工業株式会社 Pyrazole derivatives and pest control agents
JP2012188418A (en) 2011-02-22 2012-10-04 Nissan Chem Ind Ltd Triazole derivative, and pest control agent
TW201238487A (en) 2011-02-25 2012-10-01 Dow Agrosciences Llc Pesticidal compositions and processes related thereto
JP2013107867A (en) 2011-04-21 2013-06-06 Nissan Chem Ind Ltd Pyrazole derivative and pest controlling agent
WO2012147107A2 (en) 2011-04-29 2012-11-01 Msn Laboratories Limited Novel & improved processes for the preparation of indoline derivatives and its pharmaceutical composition
EP2532661A1 (en) 2011-06-10 2012-12-12 Syngenta Participations AG Novel insecticides
EP2540718A1 (en) 2011-06-29 2013-01-02 Syngenta Participations AG. Novel insecticides
CA2841450C (en) 2011-07-12 2019-04-23 Dow Agrosciences Llc Pesticidal compositions and processes related thereto
EA201400138A1 (en) 2011-07-15 2014-06-30 Басф Се PESTICIDAL METHODS OF USING SUBSTITUTED 3-Pyridylthiazol Compounds and Derivatives to Combat Animal Pests II
JP2013075871A (en) 2011-09-30 2013-04-25 Nissan Chem Ind Ltd Thiazole derivative and pest controller
JP2013082699A (en) 2011-09-30 2013-05-09 Nissan Chem Ind Ltd Pyrazole derivative and pest control agent
JP2013082704A (en) 2011-09-30 2013-05-09 Nissan Chem Ind Ltd Thiazole derivative and pest control agent
KR102006039B1 (en) * 2011-10-26 2019-07-31 다우 아그로사이언시즈 엘엘씨 Pesticidal compositions and processes related thereto
US20140296068A1 (en) 2011-10-26 2014-10-02 Dow Agrosciences Llc Pesticidal compositions and processes related thereto
DE102011085492A1 (en) 2011-10-31 2013-05-02 Evonik Goldschmidt Gmbh New amino group-containing siloxanes, process for their preparation and use
JP2013129651A (en) 2011-11-22 2013-07-04 Nissan Chem Ind Ltd Thiazole derivative and pest control agent
JP2013129653A (en) 2011-11-22 2013-07-04 Nissan Chem Ind Ltd Triazole derivative and pest control agent
WO2013156431A1 (en) 2012-04-17 2013-10-24 Syngenta Participations Ag Pesticidally active pyridyl- and pyrimidyl- substituted thiazole and thiadiazole derivatives
WO2013156433A1 (en) 2012-04-17 2013-10-24 Syngenta Participations Ag Insecticidally active thiazole derivatives
NZ700590A (en) 2012-04-27 2016-03-31 Dow Agrosciences Llc Pesticidal compositions and processes related thereto
BR112014030091B1 (en) 2012-06-04 2019-01-15 Dow Agrosciences Llc processes for producing certain 2- (pyridin-3-yl) thiazoles
US9198428B2 (en) 2012-06-04 2015-12-01 Dow Agrosciences, Llc. Processes to produce certain 2-(pyridine-3-yl)thiazoles
US9108932B2 (en) 2013-03-13 2015-08-18 Dow Agrosciences Llc Preparation of haloalkoxyarylhydrazines and intermediates therefrom
WO2015058021A1 (en) 2013-10-17 2015-04-23 Dow Agrosciences Llc Processes for the preparation of pesticidal compounds
CA2926095A1 (en) 2013-10-17 2015-04-23 Dow Agrosciences Llc Processes for the preparation of pesticidal compounds
CN105636441B (en) 2013-10-17 2018-06-15 美国陶氏益农公司 The method for preparing Pesticidal compound
CA2925954A1 (en) 2013-10-17 2015-04-23 Dow Agrosciences Llc Processes for the preparation of pesticidal compounds
WO2015058022A1 (en) 2013-10-17 2015-04-23 Dow Agrosciences Llc Processes for the preparation of pesticidal compounds
CN105636446B (en) 2013-10-17 2018-07-13 美国陶氏益农公司 The method for preparing Pesticidal compound
EP3057425A4 (en) 2013-10-17 2017-08-02 Dow AgroSciences LLC Processes for the preparation of pesticidal compounds
AR098110A1 (en) 2014-07-31 2016-05-04 Dow Agrosciences Llc PROCESS FOR THE PREPARATION OF 3- (3-CHLORINE-1H-PIRAZOL-1-IL) PIRIDINE
CA2954345A1 (en) 2014-07-31 2016-02-04 Dow Agrosciences Llc Process for the preparation of 3-(3-chloro-1h-pyrazol-1-yl)pyridine
WO2016018444A1 (en) 2014-07-31 2016-02-04 Dow Agrosciences Llc Process for the preparation of 3-(3-chloro-1h-pyrazol-1-yl)pyridine
CA2958058A1 (en) 2014-08-19 2016-02-25 Dow Agrosciences Llc Process for the preparation of 3-(3-chloro-1h-pyrazol-1-yl)pyridine
BR112017004613A2 (en) 2014-09-12 2017-12-05 Dow Agrosciences Llc Process for the preparation of 3- (3-chloro-1h-pyrazol-1-yl) pyridine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1373662A (en) * 1999-08-12 2002-10-09 法玛西雅意大利公司 3(5)-amino-pyrazole derivs., process for their preparation and their use as antitumor agents
WO2012061290A2 (en) * 2010-11-03 2012-05-10 Dow Agrosciences Llc Pesticidal compositions and processes related thereto

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110325036A (en) * 2016-12-29 2019-10-11 美国陶氏益农公司 The method for being used to prepare Pesticidal compound
CN110325036B (en) * 2016-12-29 2021-10-26 美国陶氏益农公司 Process for preparing pesticidal compounds

Also Published As

Publication number Publication date
EP3057428A1 (en) 2016-08-24
WO2015058023A1 (en) 2015-04-23
US20150112075A1 (en) 2015-04-23
US20160115135A1 (en) 2016-04-28
US20150252004A1 (en) 2015-09-10
MX2016004946A (en) 2016-06-28
US20160368880A1 (en) 2016-12-22
US9670164B2 (en) 2017-06-06
US20170233367A1 (en) 2017-08-17
JP2016535008A (en) 2016-11-10
US9908864B2 (en) 2018-03-06
CN105636446B (en) 2018-07-13
KR20160074542A (en) 2016-06-28
US9085564B2 (en) 2015-07-21
EP3057428A4 (en) 2017-05-17
IL245066A0 (en) 2016-06-30
CA2925952A1 (en) 2015-04-23
US9447048B2 (en) 2016-09-20
US9260396B2 (en) 2016-02-16

Similar Documents

Publication Publication Date Title
CN105636446A (en) Herbicidal composition comprising acc inhibitors
CN105636444A (en) Processes for the preparation of pesticidal compounds
CN105636440A (en) Processes for the preparation of pesticidal compounds
CN105636442A (en) Processes for the preparation of pesticidal compounds
CN105636445B (en) The method for preparing Pesticidal compound
US9670178B2 (en) Processes for the preparation of pesticidal compounds
CN105636443A (en) Processes for the preparation of pesticidal compounds
CN109879867B (en) Preparation and application of pyrazole oxime ether compound containing 5-aryl oxazole structure
KR100920771B1 (en) New Fluorine-containing Phenylformamidine Derivatives and Their Use as Insecticide

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20180713

Termination date: 20181017